肝内胆管癌穿刺标本组织学分型的免疫组化分类模型构建及诊断价值

摘要/Abstract

摘要： 目的分析免疫组化标志物在不同组织学分型肝内胆管癌(intrahepatic cholangiocarcinoma, ICC)中的表达差异,筛选适用于肝穿刺活检标本的最佳免疫组化标志物组合方案,以辅助ICC组织学分型。方法回顾性收集2019年12月至2021年12月复旦大学附属中山医院未经治疗且行手术切除的ICC病例214例,明确病理分型。采用免疫组化技术检测ICC病理分型常用标志物S-100P、CD56、MUC5AC、CRP、TFF-1及N-cadherin的表达,通过受试者工作特征(ROC)曲线及曲线下面积(AUC)评估诊断效能,探索针对ICC肝穿刺活检标本病理分型的最佳免疫组化组合方案。收集2022年1月至2023年10月诊断为ICC的肝穿刺活检及其配对手术切除病例共77对,验证免疫组化分类模型有效性。结果手术标本中,S-100P、MUC5AC及TFF-1主要表达于大胆管型ICC(P<0.001),CD56、CRP及N-cadherin主要表达于小胆管型ICC(P<0.001)。多标志物联合检测显著优于单标志物检测(P<0.05)。在大胆管型ICC中,S-100P、MUC5AC和TFF-1三种标志物联合检测诊断最佳(AUC=0.943,95%CI:0.913~0.974),TFF-1与S-100P联合检测AUC与三者联合AUC差异无统计学意义(P=0.062);在小胆管型ICC中,CD56、CRP和N-cadherin三种标志物联合检测诊断最佳(AUC=0.889,95%CI:0.842~0.937),CD56与CRP联合检测AUC与三者联合AUC差异无统计学意义(P=0.099)。以S-100P、CD56、TFF-1及CRP构建的免疫组化分类模型为最优组合方案。该模型结合组织形态对肝穿刺活检标本的分型结果与术后标本病理分型具有高度一致性(κ=0.814,P<0.001)。结论基于S-100P、CD56、TFF-1及CRP的免疫组化分类模型对ICC的组织学分型有较高诊断价值,有助于肝穿刺活检精准病理诊断,为临床诊疗方案的制定提供依据。

关键词: 肝内胆管癌, 肝穿刺, 免疫组织化学, 组织学分型

Abstract: Objective To investigate the optimal immunohistochemical panel for subclassifying intrahepatic cholangiocarcinoma (ICC) into small- and large-duct types from liver biopsy specimens by evaluating the expression of S-100P, CD56, MUC5AC, CRP, TFF-1, and N-cadherin. Methods Two hundred and fourteen surgical cases of ICC diagnosed by the department of pathology of Zhongshan Hospital Affiliated to Fudan University from December 2019 to December 2021 were retrospectively analyzed. The expression of S-100P, CD56, MUC5AC, CRP, TFF-1, and N-cadherin was detected by immunohistochemistry. An immunohistochemical panel with maximum diagnostic efficacy for histological classification in liver biopsy specimens was explored based on receiver operating characteristic curve (ROC) and area under curve (AUC) analyses. Seventy-seven paired puncture biopsy specimens and surgical resection specimens diagnosed as ICC from January 2022 to March 2023 were collected to verify the accuracy and consistency of the classification panel. Results In surgical specimens, S-100P, MUC5AC, and TFF-1 were mainly expressed in large-duct ICC (P<0.001), while CD56, CRP, and N-cadherin were mainly expressed in small-duct ICC (P<0.001). The combined detection of multiple biomarkers could improve the diagnostic accuracy when compared to any of the single biomarker (P<0.05). For large-duct type ICC, the panel of S-100P/MUC5AC/TFF-1 demonstrated optimal efficacy in diagnosis (AUC=0.943,95%CI:0.913~0.974), no significant statistical difference was observed between the combined TFF-1/S-100P and the triple panel (P=0.062); For small-duct type ICC, the panel of CD56/CRP/N-cadherin achieved optimal efficacy in the diagnosis (AUC=0.889,95%CI:0.842~0.937), while no significant statistical difference was observed between the combined CD56/CRP panel and the triple panel(P=0.099). The immunohistochemical panel of S-100P, CD56, TFF-1, and CRP presented the optimal classification model, which reached a strong consistency between biopsy pathology and surgical pathology (κ=0.814,P<0.001). Conclusion The immunohistochemical panel of S-100P, CD56, TFF-1, and CRP has maximum diagnostic efficacy for the histological classification of ICC in liver biopsy specimens, which provides a pathological basis for the clinical diagnosis and treatment.

Key words: Intrahepatic cholangiocarcinoma, Liver biopsy specimens, Immunohistochemistry, Classification

王语林, 纪元, 郭欣欣, 韩晶, 张欣. 肝内胆管癌穿刺标本组织学分型的免疫组化分类模型构建及诊断价值[J]. 肝脏, 2026, 31(6): 816-821.

Wang Yulin, Ji Yuan, Guo Xinxin, Han Jing, Zhang Xin. The significance of an immunohistochemical panel in histological classification of intrahepatic cholangiocarcinoma in liver biopsy specimens[J]. Chinese Hepatolgy, 2026, 31(6): 816-821.

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